With the increasing demands for foods and other agriculture-based products, sustainable agricultural practices are the cornerstone for improving low-input agricultural production. In contrast to crop production, plant-microorganism interaction (PMI) plays a crucial role. PMI significantly raises productivity as well as maintaining the overall health of the crop. During harsh and extreme physiological conditions, plant-associated extremophilic microbes (PAEM) are known to contribute to crop production, survivability, and fitness. Thus, the application of extremophiles either in the form of biofertilizer or biopesticides is highly beneficial. Extremophiles have been adapted to withstand diverse harsh environmental conditions. They possess unique mechanisms at the molecular level to produce enormous potential extremozymes and bioactive compounds. Consequently, extremophiles represent the foundation of efficient and sustainable agriculture. This chapter introduces the significance and application of plant-associated extremophilic microbes in sustainable agriculture.